Chalcones as potent antiplatelet agents and calcium channel blockers

Abstract

Abstract In an effort to continually develop potent antiplatelet agents with vasorelaxing and antiinflammatory actions, a novel series of antiinflammatory chalcones was continually screened to evaluate their antiplatelet and vasorelaxing effects. Their structure–activity relationships and mode of action were discussed and characterized. A novel series of antiinflammatory chalcones was studied on antiplatelet effect in rabbit washed platelets and human platelet‐rich plasma (PRP) and vasorelaxing effect in rat thoracic aorta. Arachidonic acid‐induced platelet aggregation was potently inhibited by almost all the chalcone derivatives and 13–15 also had a potent inhibitory effect on cyclooxygenase. The selective chalcones 12–16 tested in human PRP significantly inhibited secondary aggregation induced by adrenaline. In rat thoracic aorta, most of chalcones at high concentration significantly depressed the contractions induced by Ca 2+ (1.9 mM) in high K + (80 mM) medium and the phasic and tonic contractions caused by norepinephrine (3 μM). In the rat thoracic aorta, the phenylephrine‐ and high K + ‐induced 45 Ca 2+ influx were both inhibited by a selective chalcone derivative, 14 . These results indicate that the antiplatelet actions of chalcones are mainly mediated through the suppression of cyclooxygenase activity and reduced thromboxane formation and their inhibitory effects on the contractile response caused by high K + and norepinephrine in rat thoracic aorta are mainly due to inhibition of Ca 2+ influx through both voltage‐dependent and receptor‐operated Ca 2+ channels. Drug Dev. Res. 53:9–14, 2001. © 2001 Wiley‐Liss, Inc.